Instrumental validation of free water, peak-width of skeletonized mean diffusivity, and white matter hyperintensities: MarkVCID neuroimaging kits

Alzheimers Dement (Amst). 2022 Mar 28;14(1):e12261. doi: 10.1002/dad2.12261. eCollection 2022.


Introduction: To describe the protocol and findings of the instrumental validation of three imaging-based biomarker kits selected by the MarkVCID consortium: free water (FW) and peak width of skeletonized mean diffusivity (PSMD), both derived from diffusion tensor imaging (DTI), and white matter hyperintensity (WMH) volume derived from fluid attenuation inversion recovery and T1-weighted imaging.

Methods: The instrumental validation of imaging-based biomarker kits included inter-rater reliability among participating sites, test-retest repeatability, and inter-scanner reproducibility across three types of magnetic resonance imaging (MRI) scanners using intra-class correlation coefficients (ICC).

Results: The three biomarkers demonstrated excellent inter-rater reliability (ICC >0.94, P-values < .001), very high agreement between test and retest sessions (ICC >0.98, P-values < .001), and were extremely consistent across the three scanners (ICC >0.98, P-values < .001).

Discussion: The three biomarker kits demonstrated very high inter-rater reliability, test-retest repeatability, and inter-scanner reproducibility, offering robust biomarkers suitable for future multi-site observational studies and clinical trials in the context of vascular cognitive impairment and dementia (VCID).

Keywords: VCID; biomarker; diffusion tensor imaging; free water; magnetic resonance imaging; peak‐width skeletonized mean diffusivity; small vessel disease; vascular contributions to cognitive impairment and dementia; white matter hyperintensity; white matter injury.